The overall objective of this proposed research is to evaluate the validity, reliability and repeatability of polarization sensitive optical coherence tomography (PS-OCT) as a non-invasive optical device for the accurate and early clinical assessment of tooth demineralization and remineralization. The central hypothesis underlying this proposal is that depth-resolved changes in the magnitude of light scattering of dental hard tissues at 1310-nm, that occur upon demineralization and remineralization, can be imaged and quantified in vivo using PS-OCT and that those changes can be correlated with the structural changes and relative mineral loss measured using polarized-light microscopy and microradiography. The overall objective of this proposal will be achieved through the following specific aims. (1) To assemble and test a hand-held scanner incorporating a high-resolution probe for the clinical imaging of surface and sub-surface demineralization using PS-OCT. (2): To test the hypothesis that PS-OCT can be used to measure and quantify the early demineralization and remineralization of enamel, dentin and cementum in vitro using simulated caries models and natural lesions on extracted teeth. (3): To validate PS-OCT for the accurate and early clinical assessment of tooth surface and sub-surface demineralization by in vivo measurements using the hand-held scanner assembled and tested in aim#1. These studies and future clinical studies including those involving the important occlusal and root surfaces and those involving both tooth demineralization and remineralization will validate PS-OCT as a clinical tool for the accurate and early clinical assessment of tooth demineralization and remineralization. This is expected to lead to the clinical implementation of PS-OCT for the assessment and monitoring of the activity and severity of early carious lesions without the use of ionizing radiation, leading to an increased efficiency of caries clinical trials and a marked reduction in their scope and cost. Moreover, it is highly probable that this proposed imaging technology would enable the clinician to detect and quantify the severity of occlusal lesions in enamel that are not resolvable with conventional radiography due to attenuation by the surrounding sound tissue structure. This latter benefit would be a major advance in preventive dentistry as it would signal the need for early chemical therapeutic intervention and be able to monitor the subsequent success of that intervention. [unreadable] [unreadable] [unreadable]